Pathogenic mutations in the hydrophobic core of the human prion protein can promote structural instability and misfolding.

ABSTRACT: Transmissible spongiform encephalopathies, or prion diseases, are caused by misfolding and aggregation of the prion protein PrP. These diseases can be hereditary in humans and four of the many disease-associated missense mutants of PrP are in the hydrophobic core: V180I, F198S, V203I and V210I. The T183A mutation is related to the hydrophobic core mutants as it is close to the hydrophobic core and known to cause instability. We used extensive molecular dynamics simulations of these five PrP mutants to compare their dynamics and conformations to those of the wild type PrP. The simulations highlight the changes that occur upon introduction of mutations and help to rationalize experimental findings. Changes can occur around the mutation site, but they can also be propagated over long distance

SUBMITTER: van der Kamp MW 

PROVIDER: S-EPMC2994014 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature